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An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin

An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin

Dyer, Paul D. R., Kotha, Arun K., Gollings, Alex S., Shorter, Susan A., Shepherd, Thomas R., Pettit, Marie W., Alexander, Bruce D., Getti, Giulia T. M., El-Daher, Samer, Baillie, Les and Richardson, Simon C. W. (2016) An in vitro evaluation of epigallocatechin gallate (eGCG) as a biocompatible inhibitor of ricin toxin. Biochimica et Biophysica Acta (BBA) - General Subjects, 1860 (7). pp. 1541-1550. ISSN 0304-4165 (doi:10.1016/j.bbagen.2016.03.024)

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Abstract

The catechin, epigallocatechin gallate (eGCG), found in green tea, has inhibitory activity against a number of protein toxins and was investigated in relation to its impact upon ricin toxin (RT) in vitro. The IC50 for RT was 0.08±0.004ng/mL where as the IC50 for RT + 100μM eGCG was 3.02±0.572ng/mL, indicating that eGCG mediated a significant (p<0.0001) reduction in ricin toxicity. This experiment was repeated in the human macrophage cell line THP-1 and IC50 values were obtained for RT (0.54±0.024ng/mL) and RT + 100μM eGCG (0.68±0.235ng/mL) again using 100μM eGCG and was significant (p=0.0013). The documented reduction in ricin toxicity mediated by eGCG was found to be eGCG concentration dependent, with 80 and 100μg/mL (i.e. 178 and 223μM respectively) of eGCG mediating a significant (p=0.0472 and 0.0232) reduction in ricin toxicity at 20 and 4ng/ml of RT in Vero and THP-1 cells (respectively). When viability was measured in THP-1 cells by propidium iodide exclusion (as opposed to the MTT assays used previously) 10ng/mL and 5ng/mL of RT was used. The addition of 1000μM and 100μM eGCG mediated a significant (p=0.0015 and <0.0001 respectively) reduction in ricin toxicity relative to an identical concentration of ricin with 1μg eGCG. Further, eGCG (100μM) was found to reduce the binding of RT B chain to lactoseconjugated Sepharose as well as significantly (p=0.0039) reduce the uptake of RT B chain in Vero cells. This data suggests that eGCG may provide a starting point to refine biocompatible substances that can reduce the lethality of ricin.

Item Type: Article
Additional Information: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: Ricin toxin; Endocytosis; Polyphenol; Epigallocatechin gallate; eGCG; Tea
Subjects: R Medicine > RC Internal medicine > RC1200 Sports Medicine
Faculty / Department / Research Group: Faculty of Engineering & Science
Faculty of Engineering & Science > Department of Life & Sports Sciences
Last Modified: 28 Apr 2018 22:42
Selected for GREAT 2016: GREAT a
Selected for GREAT 2017: None
Selected for GREAT 2018: None
URI: http://gala.gre.ac.uk/id/eprint/14755

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